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Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology

Vanderbilt-Pittsburgh Resource for Organotypic Models for Predictive Toxicology
  2. Project 1 - Mammosphere Chip

Project 1 - Mammosphere Chip


Professor Lisa McCawley is the Co-PI for Project 1 "Mammosphere Bioreactor For Life-Stage Specific Toxicology". Her team is developing a microfluidic mammary gland organotypic culture model (MG OCM) for toxicant assessment, monitoring of dynamic toxicant-dependent changes to cellular functions and signaling cascades, and elucidation of Adverse Outcome Pathways.

Background: In vivo the mammary gland is particularly sensitive to toxicant exposures during different life stages co-incident with times of active tissue growth and remodeling. We propose to extend our previously developed, microfabricated Mammary Gland Thick Tissue Bioreactor (MG-TTB) to support the combination of 3D culture methods with controlled exposure to investigate chemicals for potential mammary gland toxicity. The TTB system offers significant advantages over traditional 3D cell culture, allowing for decreased reagent use and physiologically relevant microenvironments.

 

Mammary Gland

Mammary gland bioreactor prototype

Aim 1: To develop and validate the predictive utility of self-contained, fully-automated MG OCM modules.
Aim 2: To investigate the effects of chemical exposures on MG OCMs for chemicals shown to reduce lactation index in only the F2 generation of multigenerational studies – strongly suggesting a role for life-stage specific exposure.
Aim 3: To develop and validate toxicant assessment for compounds requiring metabolic activation using a paired Liver-OCM/MG-OCM.

 

 

Here is a link to our publicly accessible, annual report of Research Project Results.